Iron-Catalyzed Parahydrogen Induced Polarization

Parahydrogen induced polarization (PHIP) can address the low sensitivity problem intrinsic to nuclear magnetic resonance spectroscopy. Using a catalyst capable of reacting with parahydrogen and substrate in either a hydrogenative or nonhydrogenative manner can result in signal enhancement of the substrate. This work describes the development of a rare example of an iron catalyst capable of reacting with parahydrogen to hyperpolarize olefins. Complexes of the form (MesCCC)Fe(H)(L)(N2) (L = Py (Py = pyridine), PMe3, PPh3) were synthesized from the reaction of the parent complexes (MesCCC)FeMes(L) (Mes = mesityl) with H2. The isolated low-spin iron(II) hydride compounds were characterized via multinuclear NMR spectroscopy, infrared spectroscopy, and single crystal X-ray diffraction. (MesCCC)Fe(H)(Py)(N2) is competent in the hydrogenation of olefins and demonstrated high activity toward the hydrogenation of monosubstituted terminal olefins. Reactions with p-H2 resulted in the first PHIP effect mediated by iron which requires diamagnetism throughout the reaction sequence. This work represents the development of a new PHIP catalyst featuring iron, unlocking potential to develop more PHIP catalysts based on first-row transition metals.

General Considerations.All manipulations of air-and moisture-sensitive compounds were carried out in the absence of water and dioxygen in an MBraun inert atmosphere glovebox under a dinitrogen atmosphere except where specified otherwise.All glassware was oven dried for a minimum of 8 h and cooled in an evacuated antechamber prior to use in the glovebox.Solvents for sensitive manipulations were dried and deoxygenated on a Glass Contour System (SG Water USA, Nashua, NH) and stored over 4 Å molecular sieves purchased from Strem following a literature procedure prior to use. 1 The complexes ( Mes CCC)FeMes(L) (L = pyridine, PMe3, PPh3) were prepared according to literature procedure. 2Benzene-d6 and THF-d8 were purchased from Cambridge Isotope Labs and were degassed and stored over 4 Å molecular sieves prior to use.Celite® 545 (J.T. Baker) was dried in a Schlenk flask for 24 h under dynamic vacuum while heating to at least 150˚C prior to use in a glovebox.NMR Spectra were recorded at room temperature on a Bruker spectrometer equipped with a Prodigy probe and a SampleXpress autosampler operating at 600 MHz ( 1 H), 151 MHz ( 13 C), and 243 MHz ( 31 P) and referenced to the residual solvent resonance (δ in parts per million, and J in Hz).Solid-state infrared spectra were recorded using a PerkinElmer Frontier FT-IR spectrophotometer equipped with a KRS5 thallium bromide/iodide Universal Attenuated Total Reflectance accessory.Elemental analyses were performed at the University of Illinois at Urbana-Champaign School of Chemical Sciences Microanalysis Laboratory in Urbana, IL.Mass Spectrometry analyses were performed at the University of Illinois at Urbana-Champaign Mass Spectrometry Laboratory.X-ray crystallography was performed at the George L. Clark X-ray Facility at UIUC.Single-crystal X-ray diffraction data were collected with the use of multimirror monochromatized Mo Kα radiation (0.71073 Å) at 100 K on a Bruker D8 Venture diffractometer equipped with a Photon 100 detector.Combinations of 0.5° φ and ω scans were used to collect the data.The collection, cell refinement, and integration of intensity data were carried out with the APEX2 software. 3Multi-scan absorption correction was performed using SADABS. 4The structures were solved with XT 5 and refined with the full-matrix least-squares SHELXL 6 program within the Olex2 7 refinement GUI.All structures were submitted to the Cambridge Structural Database.

Synthesis of Metal Complexes
Synthesis of ( Mes CCC)Fe(H)(Py)(N2) (2-Py).A 15 mL Schlenk flask equipped with a stir bar was charged with ( Mes CCC)FeMes(Py) (0.050 g, 0.063 mmol, 1.0 equiv.)and THF (2 mL).The flask was taken out of the glovebox and subjected to two freeze-pump-thaw cycles prior to addition of 1 atm of H2 at 77 K.The flask was reintroduced to the glovebox and set to stir for 4 h, exhibiting a color change from dark purple to dark red.Afterwards, the solution was filtered over Celite.Volatiles were removed under reduced pressure and the solid residue was washed with cold HMDSO (2 x 2 mL) followed by extraction in hexanes.After removal of volatiles under reduced pressure, the product was obtained as a dark red powder in moderate yield (0.033 g, 0.046 mmol, 74%).Crystals suitable for X-ray diffraction were grown from a concentrated hexanes solution of the product at -35 °C.Anal

Synthesis of ( Mes CCC)Fe(H)(PPh3)(N2) (2-PPh3
).A 15 mL Schlenk flask equipped with a stir bar was charged with ( Mes CCC)FeMes(PPh3) (0.040 g, 0.041 mmol, 1.0 equiv.)and THF (4 mL).The flask was taken out of the glovebox and subjected to two freeze-pump-thaw cycles prior to addition of 1 atm of H2 at 77 K.The flask was reintroduced to the glovebox and set to stir overnight to ensure full conversion.After stirring, the solution was filtered over Celite and volatiles removed under reduced pressure.The solid residue was washed with HMDSO (3 x 3 mL) and diethyl ether (2 x 1 mL), and lyophilized from benzene to give a bright orange powder in good yield (0.030 g, 0.034 mmol, 83%).Crystals suitable for X-ray diffraction were grown from a concentrated diethyl ether solution of the product with 1 drop of HMDSO.Anal.Calcd.for C56H49FeN6P: C, 75.

Figure S19 1 H
Figure S19 1 H NMR spectrum of the reaction of styrene with D2 (4 atm) in the presence of 2-Py in C6D6 after 2 h.Inset shows the formation of H2 and HD gas under catalytic conditions.

Figure S22 1 H
Figure S22 1 H NMR spectra of the stoichiometric reaction of 1-octene and 2-Py in C6D6 after 30 min (bottom) and 2 h (top).Inset shows the relevant olefinic resonances of 1-octene at 5.01 ppm and the isomerization products between 5.36-5.51ppm.The 1-octene resonance HC overlaps with a triplet in 2-Py that is observed after the reaction.

Figure S23 Normalized single transient 1 H
Figure S23 Normalized single transient 1 H NMR spectra of the reaction of styrene with p-H2 (4 atm) in the presence of 2-Py.Bottom spectrum was collected immediately following addition of p-H2, while the top spectrum was taken after full relaxation of the nuclear spins back to thermal equilibrium amplified by a factor of 10.

Figure S24
Figure S24 One-transient array of 1 H NMR spectra showing the decay of polarization of styrene in the reaction with p-H2 and 2-Py at the 50G fringe line of the magnet and with a 45° pulse.Bottom spectrum was collected immediately after shaking the sample and inserting into the instrument, followed by an acquisition time of 4.096 s before collection of each subsequent transient.Sample was only shaken once.(*)Denotes THF

Figure S26
Figure S26 One-transient array of 1 H NMR spectra showing the decay of polarization of 4methoxystyrene in the reaction with p-H2 and 2-Py at the 50G fringe line of the magnet and with a 45° pulse.Bottom spectrum was collected immediately after shaking the sample and inserting into the instrument, followed by an acquisition time of 4.096 s before collection of each subsequent transient.Sample was only shaken once.(*)Denotes THF

Figure S28
Figure S28 One-transient array of 1 H NMR spectra showing the decay of polarization of 4fluorostyrene in the reaction with p-H2 and 2-Py at the 50G fringe line of the magnet and with a 45° pulse.Bottom spectrum was collected immediately after shaking the sample and inserting into the instrument, followed by an acquisition time of 4.096 s before collection of each subsequent transient.Sample was only shaken once.(*)Denotes THF

Figure S30
Figure S30 One-transient array of 1 H NMR spectra showing the decay of polarization of 1octene in the reaction with p-H2 and 2-Py at the 50G fringe line of the magnet and with a 45° pulse.Bottom spectrum was collected immediately after shaking the sample and inserting into the instrument, followed by an acquisition time of 4.096 s before collection of each subsequent transient.Sample was only shaken once.(*)Denotes THF